PLAAT5 is a calcium-independent phospholipase and acyltransferase that catalyzes two complementary lipid-modifying reactions. It exhibits phospholipase A1/A2 activity, releasing fatty acids from the sn-1 or sn-2 positions of glycerophospholipids 1. Functionally, PLAAT5 catalyzes N-acylation of phosphatidylethanolamine (PE) using fatty acyl groups from phosphatidylcholine, generating N-acylphosphatidylethanolamine (NAPE) 2. This reaction initiates the biosynthetic pathway for bioactive N-acylethanolamines (NAEs), including the endocannabinoid anandamide and anti-inflammatory N-palmitoylethanolamine, which regulate food intake, pain, inflammation, and stress responses. At the genetic level, PLAAT5 variants are suggestively associated with Parkinson's disease risk in large Chinese population cohorts 3. Pharmacologically, PLAAT5 represents a therapeutic target; the pan-PLAAT inhibitor LEI-301 potently reduces NAE levels in cells overexpressing PLAAT5 4, suggesting potential therapeutic applications in conditions involving dysregulated endocannabinoid or NAE signaling.